Mykophenolatmofetil: eine neue Therapieoption bei neuroimmunologischen Erkrankungen

Zusammenfassung

Mykophenolatmofetil (MMF) erweitert das Spektrum immunmodulatorischer Substanzen, die in der Therapie neuroimmunologischer Erkrankungen eingesetzt werden können. Bisher sind positive therapeutische Effekte bei Myasthenia gravis, Myositiden, autoimmunen Polyneuropathien, multipler Sklerose und zerebraler Vaskulitis beschrieben worden. Das Spektrum möglicher Indikationen für die Verabreichung von MMF auf neurologischem Fachgebiet ist aktuell noch nicht abschließend definiert. Die Indikation für den „Off-label”-Einsatz von MMF muss im Einzelfall sorgfältig geprüft werden. Bei Myasthenia gravis konnten sowohl retrospektive Analysen als auch eine offene Studie und eine randomisierte plazebokontrollierte Studie die Wirksamkeit und gute Verträglichkeit belegen. MMF scheint daher eine mögliche therapeutische Alternative zu Azathioprin oder Ciclosporin A bei Unverträglichkeiten oder unzureichender Wirksamkeit zu sein. Weitere kontrollierte Studien sind notwendig, um die Kurz- und Langzeiteffekte von MMF bei neuroimmunologischen Erkrankungen genauer zu evaluieren.

Abstract

Mycophenolate mofetil (MMF) is a novel immunosuppressive drug and has been applied in myasthenia gravis, dysimmune polyneuropathies, myositis, multiple sclerosis and cerebral vasculitis. The spectrum of neurological diseases in which MMF may be effective is not finally delineated. So far, only in myasthenia gravis the efficacy and safety of MMF has been evaluated by retrospective analyses, one open-label study and one placebo-controlled double blind study. In myasthenia gravis, replacement of azathioprine or cyclosporine A by MMF seems to be useful in non-responders or in case of intolerance. Further controlled studies are necessary to evaluate short-term and long-term effects of MMF in neurological autoimmune diseases.

Literatur

• 1 Kim Y S, Moon J I, Kim S I, Park K. Clear benefit of mycophenolate mofetil-based triplet therapy in reducing the incidence after living donor renal transplantation.  Transplantation. 1999;  68 578-581
• 2 Enk A H, Knop J. Treatment of pemphigus vulgaris with mycophenolate mofetil.  Lancet. 1997;  350 494
• 3 Epinette W W, Parker C M, Jones E l, Greist M C. Mycophenolic acid for psoriasis. A review of pharmacology, long-term efficacy, and safety.  J Am Acad Dermatol. 1987;  17 962-971
• 4 Larkin G, Lightman S. Mycophenolate mofetil. A useful immunosuppressive in inflammatory eye disease.  Ophthalmology. 1999;  106 370-374
• 5 Goldblum R. Treatment of rheumatoid arthritis with mycophenolate mofetil.  Clin Exp Rheumatol. 1993;  11 (Suppl 8) S117-S119
• 6 Nowack R, Göbel U, Klooker P. et al . Mycophenolate mofetil for maintenance therapy of Wegener's granulomatosis and microscopic polyangiitis. A pilot study in 11 patients with renal involvement.  J Am Soc Nephrol. 1999;  10 1965-1971
• 7 Neurath M F, Wanitschke R, Peters M. et al . Randomised trial of mycophenolate mofetil versus azathioprine for treatment of chronic active Crohn's disease.  Gut. 1999;  44 625-628
• 8 Hauser R A, Malek A R, Rosen R. Successful treatment of a patient with severe refractory myasthenia gravis using mycophenolate mofetil.  Neurology. 1998;  51 912-913
• 9 Schneider C, Gold R, Reiners K, Toyka K V. Mycophenolate mofetil in the therapy of severe myasthenia gravis.  Eur Neurol. 2001;  46 79-82
• 10 Chaudry V, Cornblath D R, Griffin J W. et al . Mycophenolate mofetil - a safe and promising immunosuppressant in neuromuscular diseases.  Neurology. 2001;  56 94-96
• 11 Ciafaloni E, Massey J M, Sanders D B. Preliminary results of an open label trial of cellcept in myasthenia gravis.  Neurology. 2001;  56 97-99
• 12 Mowzoon N, Sussman A, Bradley W G. Mycophenolate (CellCept) treatment of myasthenia gravis, chronic inflammatory polyneuropathy and inclusion body myositis.  J Neurol Sci. 2001;  185 119-122
• 13 Merrigioli M N, Rowin J, Richman J G, Leurgans S. Mycophenolate mofetil for myasthenia gravis: a double-blind, placebo-controlled pilot study.  Ann N Y Sci. 2003;  998 494-499
• 14 Meriggioli M N, Ciafaloni E, Al-Hayk K A. et al . Mycophenolate mofetil for myasthenia gravis: an analysis of efficacy, safety and tolerability.  Neurology. 2003;  61 1438-1440
• 15 Benedetti L, Grandis M, Nobbio L. et al . Mycophenolate mofetil in dysimmune neuropathies: a preliminary study.  Muscle Nerve. 2004;  29 748-749
• 16 Gorson K C, Amato A A, Ropper A H. Efficacy of mycophenolate mofetil in patients with chronic immune demyelinating polyneuropathy.  Neurology. 2004;  63 715-717
• 17 Ahrens N, Salama A, Haas J. Mycophenolate-mofetil in the treatment of refractory multiple sclerosis.  J Neurol. 2001;  248 713-714
• 18 Frohman E M, Brannon K, Racke M K, Hawker K. Mycophenolate mofetil in multiple sclerosis.  Clin Neuropharmacol. 2004;  27 80-83
• 19 Vermersch P, Wanquier N, Bourteel H. et al . Treatment of multiple sclerosis with a combination of interferon beta-1a (Avonex) and mycophenolate mofetil (Cellcept): results of a phase II clinical trial.  Neurology. 2004;  62 (suppl 5) A259
• 20 Gelber A C, Nousari H C, Wigley F M. Mycophenolate mofetil in the treatment of severe skin manifestations of dermatomyositis: a series of 4 cases.  J Rheumatol. 2000;  27 1542-1545
• 21 Schneider C, Gold R, Schäfers M, Toyka K V. Mycophenolate mofetil in the therapy of polymyositis associated with a polyautoimmune syndrome.  Muscle Nerve. 2002;  25 286-288
• 22 Gummert J F, Ikonen T, Morris R E. Newer immunosuppressive drugs. A review.  J Am Soc Nephrol. 1999;  10 1366-1380
• 23 Natsumeda Y, Carr S F. Human type I and II IMPDH as drug targets.  Ann NY Acad Sci. 1993;  696 88-93
• 24 Eugui E M, Mirkovich A, Allison A C. Lymphocyte-selective antiproliferative and immunosuppressive effects of mycophenolic acid in mice.  Scan J Immunol. 1991;  33 175-183
• 25 Blaheta R A, Leckel K, Wittig B. et al . Inhibition of endothelial receptor expression and T-cell ligand activity by mycophenolate mofetil.  Transpl Immunol. 1998;  6 251-259
• 26 Durez P, Apelboom T, Pira C. et al . Antiinflammatory properties of mycophenolate mofetil in murine endotoxemia: inhibition of TNF-alpha and upregulation of IL-10 release.  Int J Immunopharmacol. 1999;  21 581-587
• 27 Cohn R G, Mirkovich A, Dunlap B. et al . Mycophenolic acid increases apoptosis, lysosomes and lipid droplets in human lymphoid and monocytic cell lines.  Transplantation. 1999;  68 411-418
• 28 Lhotta K, Wurzner R, Rosenkranz A R. et al . Cerebral vasculitis in a patient with hereditary complete C4 deficiency and systemic lupus erythematodes.  Lupus. 2004;  13 139-141
• 29 Contreras G, Pardo V, Lecleq B. et al . Sequential therapies for proliferative lupus nephritis.  N Engl J Med. 2004;  350 971-980
• 30 Budde K, Glander P, Bauer S. et al . Pharmacodynamic monitoring of mycophenolate mofetil.  Clin Chem Lab Med. 2000;  38 1213-1216
• 31 European mycophenolate mofetil study group . Placebo-controlled study of mycophenolate mofetil combined with cyclosporine and corticosteroids for prevention of acute rejection.  Lancet. 1995;  345 1321-1325